Suicidality in civilian women with PTSD: Possible link to childhood maltreatment, proinflammatory molecules, and their genetic variations

Hitomi Kawanishi; Hiroaki Hori; Fuyuko Yoshida; Mariko Itoh; Mingming Lin; Madoka Niwa; Megumi Narita; Takeshi Otsuka; Keiko Ino; Risa Imai; Shin Fukudo; Toshiko Kamo; Hiroshi Kunugi; Yoshiharu Kim

doi:10.1016/j.bbih.2023.100650

Suicidality in civilian women with PTSD: Possible link to childhood maltreatment, proinflammatory molecules, and their genetic variations

Brain Behav Immun Health. 2023 Jun 5:30:100650. doi: 10.1016/j.bbih.2023.100650. eCollection 2023 Jul.

Authors

Hitomi Kawanishi^{1

2}, Hiroaki Hori¹, Fuyuko Yoshida^{1

3}, Mariko Itoh^{1

4}, Mingming Lin^{1

5}, Madoka Niwa¹, Megumi Narita¹, Takeshi Otsuka¹, Keiko Ino^{1

6}, Risa Imai^{6

7}, Shin Fukudo², Toshiko Kamo⁸, Hiroshi Kunugi^{3

9}, Yoshiharu Kim¹

Affiliations

¹ Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
² Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
³ Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁴ Center for Environmental and Health Sciences, Hokkaido University, Hokkaido, Japan.
⁵ Laboratory for Imagination and Executive Functions, RIKEN Center for Brain Science, Wako, Saitama, Japan.
⁶ Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁷ Risa Irinaka Mental Clinic, Nagoya, Japan.
⁸ Wakamatsu-cho Mental and Skin Clinic, Tokyo, Japan.
⁹ Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan.

Abstract

Background: Posttraumatic stress disorder (PTSD) is a robust risk factor for suicide. Studies have suggested an association between suicide and elevated inflammatory markers, although such evidence in PTSD is scarce. Suicide risk, PTSD, and inflammatory molecules are all shown to be associated with childhood maltreatment and genetic factors.

Methods: We examined the association between suicidal ideation/risk and inflammatory markers in 83 civilian women with PTSD, and explored the possible influence of childhood maltreatment and inflammatory genes. Suicidal ideation and risk were assessed using the Beck Depression Inventory-II and the Mini-International Neuropsychiatric Interview. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire (CTQ). Blood levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and high-sensitivity tumor necrosis factor-α were measured. Genetic polymorphisms of CRP rs2794520 and IL6 rs1800796 were genotyped.

Results: Suicidal ideation was significantly positively correlated with hsCRP (p = 0.002) and IL-6 (p = 0.015) levels. Suicide risk weighted score was significantly positively correlated with hsCRP (p = 0.016) levels. The risk alleles of CRP rs2794520 and IL6 rs1800796 leading to increased respective protein levels were dose-dependently associated with higher risk of suicide (p = 0.007 and p = 0.029, respectively). The CTQ total score was significantly correlated with suicidal ideation and risk, but not with inflammatory marker levels. Furthermore, a multivariate regression analysis controlling for PTSD severity and potential confounders revealed that rs2794520 and rs1800796, but not hsCRP or IL-6 levels, significantly predicted suicidal ideation (p < 0.001) and risk (p = 0.007), respectively.

Conclusion: Genetic variations within inflammatory genes might be useful in detecting PTSD patients at high risk of suicide.

Keywords: Childhood maltreatment; Genetic variation; Inflammation; PTSD; Suicide.